Degeralix is a GnRH receptor antagonist approved for the treatment of patients with advanced PC. There is data suggesting it might harbor a lower incidence of CVD than GnRH agonists in patients with pre-existing CVD. This lower risk may be due to its different mode of action, leading to lower levels of atherosclerotic plaque and plaque instability [4], both of which can lead to CV events.
The PRONOUNCE study primary objective is to assess the effect of degeralix vs. GnRH agonist leuprolide on risk of recurrence of major adverse CV events (MACEs = a composite of death due to any cause, non-fatal myocardial infarction [MI] or non-fatal stroke) in patients with PC and concomitant CVD. Additional objectives include PC outcomes, additional CV outcomes, patient-reported outcomes (PROs), and overall safety and tolerability. The study schema is shown in figure 1. Patients will be randomized 1:1, stratified by age (<75 vs >=75 years) and region (North America vs. other). The goal is to accrue 900 patients. There will be independent, blinded assessment of CV events by an external clinical events committee (Duke Clinical Research Institute) (Figure 2).
In summary, ADT use may increase the incidence of CV events in men with PC and pre-existing CVD. The incidence might be lower with degeralix than GnRH agonists. This trial is designed to test this hypothesis. It is currently enrolling at sites at the US, Canada, and Europe, and expanding to the rest of the world soon.
Figure 1 – Study schema:
Figure 2 – Assessment of cardiovascular events:
Clinical Trial Information: NCTO2663908
References:
1. Studer UE et al. JCO 2006;24:1868-76
2. Calais da Silva FE et al. Eur Urol 2009;55:1269-77
3. O’Farrell et al. JCO 2015l 33:1243-51
4. Crawford ED et al. J UROL 2011; 186:889-97
Presented by: Susan F. Slovin, MD, Memorial Sloan Kettering Cancer Center, New York, NY
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan, at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA